Drug-induced liver injury: what was new in 2008?

Gordon Liss, James H Lewis
Expert Opinion on Drug Metabolism & Toxicology 2009, 5 (8): 843-60

BACKGROUND: Given the number of publications appearing annually regarding drug-induced liver injury (DILI), there remains a need to concisely summarize each year's new crop of case series and reports as well as the advances in mechanisms of liver injury and in the field of pharmacogenomics relating to DILI.

OBJECTIVE: To present an up-to-date review of the past year's most important clinical studies and reports of DILI, placing them into context of previous publications.

METHODS: A Medline search was conducted of all manuscripts appearing in the fields "hepatotoxicity" and "drug-induced liver injury" during the calendar year 2008. The most clinically relevant English language case reports and studies exploring mechanisms and risk factors for DILI were then chosen for review, and supplemented with older literature where appropriate.

CONCLUSIONS: As in past years, 2008 was replete with publications dealing with virtually all facets of DILI, including updated incidence and prevalence data, as well as the latest information regarding mechanisms of liver injury. Data from the first 300 patients in the National Institute of Health-sponsored DILI Network registry of > 100 non-acetaminophen causes were presented. Antimicrobials and CNS drugs were responsible for > 60% of cases, with herbals and dietary supplements being increasingly reported. Identification of genetic predispositions to DILI is coming of age with the FDA calling for the testing of human leukocyte antigen B(*)5701 before the use of abacavir to reduce the risk of hypersensitivity reactions. Several groups emphasized the pitfalls in utilizing Roussel Uclaf Causality Assessment Method and other causality assessment methodologies, and an updated review appeared on the use of potentially hepatotoxic medications in patients with underlying liver disease.


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